Blood stem cell formation: a fishy business

Researchers at the University of Sheffield are using fluorescent zebrafish to understand the processes by which blood stem cells form. Identifying the mechanisms by which blood stem cells are created could prove vital to help treat diseases such as leukaemia and cardiovascular disease.

Dr. Robert Wilkinson, JG Graves Medical Research Fellow, in the Department of Cardiovascular Science is using the zebrafish to understand how blood stem cells form from arteries. Dr. Wilkinson gained his D.Phil in the lab of Professor Roger Patient at the University of Oxford, where he studied the signals required for blood stem cell formation in zebrafish, followed by research with Dr. Freek van Eeden here at the University of Sheffield, where he focused on the signals which specify arteries and veins.

He says, “All our adult blood cells are derived from a single cell type, the blood stem cell, also known as the haematopoietic stem cell, or HSC. These rare, but vital, cells are formed from the embryonic artery and eventually come to reside in the bone marrow where they exist through adult life.”

“For decades, HSCs have been used in regenerative therapy to successfully treat diseases such as autoimmune conditions and leukaemia, yet it is estimated that only 1 in a million bone marrow cells is actually a transplantable HSC. Some of the cells produced by HSCs are also able to repair heart tissue which has been damaged following heart attack.”

Scientists are able to modify the zebrafish embryo by fluorescently tagging any protein of interest to allow any cell expressing it to be followed in real-time, a process assisted by the observation that zebrafish embryos are translucent.

“The ways in which HSCs form in the zebrafish are highly similar to how these cells form in humans. Using zebrafish, we can directly observe both the formation of these cells and the journey which they take throughout the developing embryo. Understanding the signals and mechanisms which regulate these processes in the zebrafish will facilitate the generation of HSCs in the lab for use in treating a wide range of human diseases.”